Qiliqiangxin Capsule Modulates Calcium Transients and Calcium Sparks in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Li, Yuxin; Zhang, Zhang; Hao, Xuezeng; Yu, Tingting; Li, Sen

doi:10.1155/2022/9361077

Cited by 2 publications

(2 citation statements)

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“…Additionally, in human pluripotent stem cell‐derived cardiomyocytes, QLQX increased Ca 2+ spark frequency, amplitude and duration, indicative of enhanced Ca 2+ release 107 . Similar effects have been reported with digitalis and other plant‐derived compounds with positive inotropic actions 108 .…”

Section: Qiliqiangxin In Experimental Models Of Marked Abrupt Cardiac...supporting

confidence: 71%

Qiliqiangxin: A multifaceted holistic treatment for heart failure or a pharmacological probe for the identification of cardioprotective mechanisms?

Packer

2023

European J of Heart Fail

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The active ingredients in many traditional Chinese medicines are isoprene oligomers with a diterpenoid or triterpenoid structure, which exert cardiovascular effects by signaling through nutrient surplus and nutrient deprivation pathways. Qiliqiangxin (QLQX) is a commercial formulation of 11 different plant ingredients, whose active compounds include astragaloside IV, tanshione IIA, ginsenosides (Rb1, Rg1 and Re) and periplocymarin. In the QUEST Trial, QLQX reduced the combined risk of cardiovascular death or heart failure hospitalization (hazard ratio 0.78 [95% CI 0.68‐0.90]), based on 859 events in 3119 patients over a median of 18.2 months; the benefits were seen in patients taking foundational drugs except for SGLT2 inhibitors. Numerous experimental studies of QLQX in diverse cardiac injuries have yielded highly consistent findings. In marked abrupt cardiac injury, QLQX mitigated cardiac injury by upregulating nutrient surplus signaling through the PI3K/Akt/mTOR/HIF‐1α/NRF2 pathway; the benefits of QLQX were abrogated by suppression of PI3K, Akt, mTOR, HIF‐1α or NRF2. In contrast, in prolonged measured cardiac stress (as in chronic heart failure), QLQX ameliorated oxidative stress, maladaptive hypertrophy, cardiomyocyte apoptosis, and proinflammatory and profibrotic pathways, while enhancing mitochondrial health and promoting glucose and fatty acid oxidation and ATP production. These effects are achieved by an action of QLQX to upregulate nutrient deprivation signaling through SIRT1/AMPK/PGC‐1α and enhanced autophagic flux. In particular, QLQX appears to enhance the interaction of PGC‐1α with PPARα, possibly by direct binding to RXRα; silencing of SIRT1, PGC‐1α and RXRα abrogated the favorable effects of QLQX in the heart. Since PGC‐1α/RXRα is also a downstream effector of Akt/mTOR signaling, the actions of QLQX on PGC‐1α/RXRα may explain its favorable effects in both acute and chronic stress. Intriguingly, the individual ingredients in QLQX — astragaloside IV, ginsenosides, and tanshione IIA — share QLQX's effects on PGC‐1α/RXRα/PPARα signaling. QXQL also contains periplocymarin, a cardiac glycoside that inhibits Na+‐K+‐ATPase. Taken collectively, these observations support a conceptual framework for understanding the mechanism of action for QLQX in heart failure. The high likelihood of overlap in the mechanism of action of QLQX and SGLT2 inhibitors requires additional experimental studies and clinical trials.This article is protected by copyright. All rights reserved.

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Section: Qiliqiangxin In Experimental Models Of Marked Abrupt Cardiac...supporting

confidence: 71%

Qiliqiangxin: A multifaceted holistic treatment for heart failure or a pharmacological probe for the identification of cardioprotective mechanisms?

Packer

2023

European J of Heart Fail

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“…XFPC were provided by the preparation room of ShanxiAcademy of Traditional Chinese Medicine (Taiyuan, China). Refer to Qizhen capsule ( Guo et al, 2021 ) and Qiliqiangxin Capsule ( Li et al, 2022 ) for the preparation method of liquid medicine. Bronchial epithelial HBE cells lines were purchased from the Shanghai Cell Bank.…”

Section: Methodsmentioning

confidence: 99%

Roles of autophagy-related genes in the therapeutic effects of Xuanfei Pingchuan capsules on chronic obstructive pulmonary disease based on transcriptome sequencing analysis

et al. 2023

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Objective: Autophagy plays an important role in the occurrence and development of chronic obstructive pulmonary disease (COPD). We evaluated the effect of Xuanfei Pingchuan capsule (XFPC) on autophagy-related genes of COPD by a bioinformatics analysis and experimental verification.Methods: The best treatment duration was screened by CCK8 assays. HBE cells were divided into three groups: blank, CSE and XFPC. After intervened by XFPC, HBE cells were collected and sent to Shenzhen Huada Gene Company for transcriptome sequencing. Subsequently, differential expression analyses, target gene prediction, and function enrichment analyses were carried out. Expression changes were verified in HBE cells by real-time Quantitative PCR (RT-qPCR) and western blotting (WB).Results: The result of differential expression analysis displayed that 125 target genes of HBE cells were mainly related to mitogen-activated protein kinase (MKK) binding, interleukin 33 binding, 1-Pyrroline-5-carboxylate dehydrogenase activity, and the mitogen-activated protein kinase (MAPK) signal pathway. Among the target genes, the core genes related to autophagy obtained by maximum neighborhood component algorithm were CSF1, AREG, MAPK9, MAP3K7, and AKT3. RT-qPCR and WB methods were used to verify the result, it showed similar expression changes in CSF1, MAPK9, MAP3K7, and AKT3 in bronchial epithelial cells to those in the bioinformatics analysis.Conclusion: Through transcriptome sequencing and validation analysis, we predicted that CSF1, MAPK9, MAP3K7, and AKT3 may be the potential autophagy-related genes that play an important role in the pathogenesis of COPD. XFPC may regulate autophagy by down-regulating the expression of CSF1, MAPK9, MAP3K7, and AKT3, thus achieving the purpose of treating chronic obstructive pulmonary disease.

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Qiliqiangxin Capsule Modulates Calcium Transients and Calcium Sparks in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Cited by 2 publications

References 42 publications

Qiliqiangxin: A multifaceted holistic treatment for heart failure or a pharmacological probe for the identification of cardioprotective mechanisms?

Qiliqiangxin: A multifaceted holistic treatment for heart failure or a pharmacological probe for the identification of cardioprotective mechanisms?

Roles of autophagy-related genes in the therapeutic effects of Xuanfei Pingchuan capsules on chronic obstructive pulmonary disease based on transcriptome sequencing analysis

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